Lower Biologically Effective Dose Research Articles

Cost Analysis of MR-Guided vs. CT-Guided Radiation Therapy for Locally Advanced Pancreatic Cancer

Stereotactic magnetic resonance guided on-table adaptive radiotherapy (SMART) is an increasingly utilized radiotherapy (RT) treatment for locally advanced pancreatic cancer (LAPC), providing improved local control and overall survival with reduced toxicity. Computed tomography (CT) guided RT options include stereotactic body radiotherapy (SBRT) and hypofractionated RT with volumetric modulated arc therapy (VMAT). Currently there are no financial comparisons for MR vs CT-guided RT for LAPC. We completed a cost analysis comparing the physician and hospital charges associated with RT options for LAPC. To compare RT costs, we identified Current Procedural Terminology (CPT) codes utilized for 5-fraction SMART with adaptation (50 Gy, biological effective dose (BED) 100 Gy), 5-fraction CT-guided SBRT (33 Gy, BED 55 Gy), and 15-fraction CT-guided hypofractionated VMAT (67.5 Gy, BED 98 Gy) in a hospital-based practice setting. Physician and hospital Medicare prices associated with these codes together summarize the overall cost. We determined physician fees using the Centers for Medicare and Medicaid Services (CMS) Physician Fee Schedule Search to search the Healthcare Common Procedure Coding System (HCPCS) for "professional" costs included within "facility" costs. We determined hospital fees using the Outpatient Prospective Payment System addendum. To standardize costs, we searched for national payment amounts for the 2022 calendar year. Total cost of SMART with adaptation was 136% higher than the cost of CT-SBRT and 149% higher than the cost of hypofractionated RT. Physician fees for SMART were 173% higher and 157% higher than the fees for CT-SBRT and hypofractionated RT, respectively. Hospital fees for SMART were 129% higher and 147% higher than the fees for CT-SBRT and hypofractionated RT, respectively. The total cost of CT-SBRT was only 5% higher than cost of hypofractionated RT. The physician fees for hypofractionated RT were 6% higher than those for CT-SBRT, while the outpatient fees for CT SBRT were 7% higher than those for hypofractionated RT. With recent data demonstrating favorable efficacy and toxicity rates for SMART, practices may increasingly consider investing in this treatment modality. This is the first cost analysis comparing SMART to CT-guided SBRT and hypofractionated RT in LAPC. We demonstrate higher costs of SMART compared to CT-guided RT, attributable primarily to higher number of dosimetry calculations for this modality and for adapted fractions. We also demonstrate comparable costs of lower BED CT-guided SBRT and higher BED hypofractionated RT. Further investigation is needed to assess whether the survival benefit of SMART translates to favorable cost per quality adjusted life year.

Effect of Adequate Local Radiation Dose on Oncological Outcomes in Localized Prostate Cancer Patients Treated With Low-dose-rate Brachytherapy.

We retrospectively investigated the effect of a biologically effective dose (BED) of Low-dose rate brachytherapy (LDR-BT) and its possible interaction with androgen deprivation therapy (ADT) during LDR-BT treatment for intermediate-risk prostate cancer (PCa). A total of 693 patients with localized, intermediate-risk PCa, who underwent LDR-BT with or without supplemental external beam radiotherapy, were included in this study. We stratified patients into two groups according to BED (<180 Gy2, lower BED group; ≥180 Gy2, higher BED group) and evaluated the effect of ADT duration on the oncological outcomes of each group. In total, 431 patients received BED ≥180 Gy2. Significant differences in biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS) were observed among the non-ADT, ADT ≤3 months, and ADT >3 months subgroups of the lower BED group (p=0.005 and 0.049, respectively). However, no significant differences in BCRFS or CPFS were detected in the higher BED group (p=0.63 and 0.76, respectively). Multivariate analysis of BCR and CP in the lower BED group revealed a significant decreasing trend in the BCRFS (p for trend=0.001) and CPFS rates (p for trend=0.015) as ADT duration increased, which was associated with favorable outcomes. However, no significant trend was observed in the BCRFS or CPFS rate in the higher BED group. An adequate local radiation dose provides favorable oncological outcomes and could potentially reduce the need for long-term ADT.

The Relevance of Biologically Effective Dose for Hearing Preservation After Stereotactic Radiosurgery for Vestibular Schwannomas: A Retrospective Longitudinal Study.

Stereotactic radiosurgery has become a common treatment approach for small-to-medium size vestibular schwannomas. To evaluate relationship between time (beam-on and treatment) and risk of hearing decline after stereotactic radiosurgery for vestibular schwannomas in patients with Gardner-Robertson (GR) baseline classes I and II. This retrospective longitudinal single-center study included 213 patients with GR I and II treated between June 2010 and December 2019. Risk of passing from GR classes I and II (coded 0) to other classes III, IV, and V (coded 1) and the increase in pure tone average (continuous outcome) were evaluated using a mixed-effect regression model. Biologically effective dose (BED) was further assessed for an alpha/beta ratio of 2.47 (Gy 2.47 ). Binary outcome analysis revealed sex, dose rate, integral dose, time [beam-on time odds ratio 1.03, P = .03, 95% CI 1.00-1.06; treatment time ( P = .02) and BED ( P = .001) as relevant. Fitted multivariable model included the sex, dose rate, and BED. Pure tone average analysis revealed age, integral dose received by tumor, isocenter number, time (beam-on time odds ratio 0.20, P = .001, 95% CI 0.083-0.33) and BED ( P = .005) as relevant. Our analysis showed that risk of hearing decline was associated with male sex, higher radiation dose rate (cutoff 2.5 Gy/minute), higher integral dose received by the tumor, higher beam-on time ≥20 minutes, and lower BED. A BED between 55 and 61 was considered as optimal for hearing preservation.

Accelerated hypofractionated radiation for elderly or frail patients with a newly diagnosed glioblastoma: A pooled analysis of patient-level data from 4 prospective trials.

The standard of care for elderly or frail patients with glioblastoma (GBM) is 40 Gy in 15 fractions of radiotherapy. However, this regimen has a lower biological effective dose (BED) compared with the Stupp regimen of 60 Gy in 30 fractions. It is hypothesized that accelerated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) is safe and efficacious. Elderly or frail patients with GBM treated with 52.5 Gy in 15 fractions were pooled from 3 phase 1/2 studies and a prospective observational study. Overall survival (OS) and progression-free survival (PFS) were defined time elapsing between surgery/biopsy and death from any cause or progression of disease. Sixty-two newly diagnosed patients were eligible for this pooled analysis of individual patient data. The majority (66%) had a Karnofsky performance status (KPS) score <70. The median age was 73 years. The median OS and PFS were 10.3 and 6.9 months, respectively. Patients with KPS scores ≥70 and <70 had a median OS of 15.3 and 9.5 months, respectively. Concurrent chemotherapy was an independent prognostic factor for improved PFS and OS. Grade 3 neurologic toxicity was seen in 2 patients (3.2%). There was no grade 4/5 toxicity. This is the only analysis of elderly/frail patients with GBM prospectively treated with a hypofractionated radiation regimen that is isoeffective to the Stupp regimen. Treatment was well tolerated and demonstrated excellent OS and PFS compared with historical studies. This regimen gives the elderly/frail population an alternative to regimens with a lower BED. Randomized trials are needed to validate these results.

Does Brachytherapy Boost Improve Biochemical Control in Intermediate and High-Risk Prostate Cancer Patients Compared to External Beam Radiotherapy Alone?

<h3>Purpose/Objective(s)</h3> The purpose of this analysis was to investigate whether the combination of external beam radiotherapy (EBRT) and brachytherapy boost (EBRT+BT) is superior to EBRT alone in terms of biochemical control (BC) in the management of intermediate (IR) and high risk (HR) prostate cancer (PC) patients and whether the difference is associated with local biologically effective dose (BED) escalation. <h3>Materials/Methods</h3> We investigated 1123 patients treated for IR (24.8%) or HR PC (75.2%) with EBRT (90.7%) or EBRT+BT (9.3%) at one institution between 2003 and 2012. Kaplan-Meier curves were used to calculate biochemical control. Log-rank testing and Cox regression were used to compare results between groups. BED was calculated using α/β of 3 for PC. The majority of patients treated with EBRT received 76 Gy in 2 Gy fractions (79%, median BED = 126.7 Gy) or equivalent. The majority of patients treated with EBRT+BT received either 54 Gy in 2 Gy fractions followed by 10-11 Gy single fraction BT boost (47.6%, median BED = 133.3 Gy), or 46-50 Gy in 2 Gy fx followed by 20-21 Gy two fraction BT boost (51.4%, median BED = 171.2 Gy). <h3>Results</h3> The median age of the patients was 68-years. The 5-year BC was 79%. There was no statistically significant difference in BC between patients treated with EBRT or BT in IR (<i>P</i> = 0.74) and HR (<i>P</i> = 0.73) PC groups. There was a significant difference between patients receiving lower and higher BED (> 135 Gy) fractionation schemes in favor of higher BED, both for IR (5-y BC of 100% vs 81%, <i>P</i> = 0.02) and HR group (5-y BC of 92% vs 77%, <i>P</i> = 0.02). The BED was inversely associated with risk of BC in univariate analysis (HR = 0.98; CI95% 0.97-0.99; <i>P</i> < 0.01), and remained an independent prognostic factor in the multivariate analysis (HR = 0.97; CI95% 0.96-0.99; <i>P</i> < 0.01) along with Gleason Grade Groups score (HR = 1.18; CI95% 1.05-1.32; <i>P</i> < 0.01). <h3>Conclusion</h3> The combination of EBRT and BT boost has the potential to significantly improve biochemical control in IR and HR prostate cancer patients through local BED escalation. The improvement in BC was observed in patients receiving higher BED, as well as a significant association between BED and risk of biochemical failure.

The Impact of Ablative Doses on Survival for Patients Treated with Definitive Radiotherapy for Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (IHCC) is a rare malignancy with a rising incidence. Prognosis is poor, especially for patients who are surgically inoperable. A recent single institution retrospective study demonstrated improved local control and overall survival for patients treated with biologically effective dose (BED)>80.5 Gy, compared to those with BED ≤80.5 Gy. The purpose of this study is to investigate the impact of ablative radiotherapy doses on survival using a large cancer database registry. The National Cancer Database was queried (2004-2015) for patients with histologically-confirmed, localized IHCC treated with definitive external beam radiotherapy with or without chemotherapy. Patients treated with palliative radiotherapy dose fractionation schemes were excluded (BED <40). Patients were divided into two cohorts based on BED: BED>80.5 Gy and BED ≤80.5 Gy. Kaplan-Meier analysis evaluated overall survival (OS). Significance of Kaplan-Meier estimates of OS was determined by log-rank testing. Multivariable Cox Proportional Hazards Regression Analysis (coxph) was used to establish factors associated with OS, with BED as a continuous variable. A total of 579 patients met the inclusion criteria; median BED was 60 Gy. 481 (83%) of patients received BED ≤80.5 Gy, whereas 98 (17%) received BED >80.5 Gy. Median follow-up was 11.8 and 13.8 months for the BED ≤80.5 Gy and BED>80.5 Gy groups, respectively. Median OS was 12.5 months for the BED ≤80.5 Gy group and 14.65 months for the BED>80.5 Gy groups (log-rank p = 0.035). Coxph results can be found in Table 1. Older age, more advanced T and N stage, and lower BED as a continuous variable were significantly associated with worse OS (p<0.05 for all). Sex, presence of comorbidities and the receipt of chemotherapy were not significantly with OS. This is the largest study to do date looking at the effect of dose escalation on outcomes of definitive radiotherapy for patients treated for IHCC. Higher BED was significantly associated with better OS using both Kaplan Meier (BED ≤80.5 Gy verses BED>80.5 Gy) and as a continuous variable on coxph. Chemotherapy was not significantly associated with OS. The retrospective nature of this analysis is recognized as a limitation. Further prospective studies are warranted to confirm these findings.Abstract 3516; TableMultivariable Cox Proportional Hazards Regression Analysis ResultsHazard Ratio95% CIp-valueAge1.0151.007-1.023<0.0005Sex0.9020.750-1.0840.2713BED0.9940.990-0.9990.0108T stage1.1421.035-1.2600.0083N stage1.4601.193-1.7860.0002Chemotherapy0.8720.701-1.0850.2204No comorbidities1.0360.8445-1.2710.7355 Open table in a new tab

Stereotactic body radiation therapy in the treatment of ovarian cancer

BackgroundThis study evaluates the outcomes and toxicity of stereotactic body radiation therapy (SBRT) in ovarian cancer.MethodsThis retrospective analysis considered all patients treated with SBRT from 2009 to 2018 with a primary ovarian tumor. Follow-up included PET-CT and CT scans at 2–3 month intervals. Statistical analysis primarily consisted of univariate analysis, Cox proportional hazards analysis, and the Kaplan-Meier method.ResultsThe study included 35 patients with 98 treatments for lymph nodes (51), local recurrence (21), and de novo solid metastases (26). Median biologically effective dose (BED), gross tumor volume, and planning target volume were 38.40 Gy, 10.41 cc, and 25.21 cc, respectively. 52 lesions showed complete radiographic response, and two-year local control was 80%. Median overall survival (OS) was 35.2 months, and two-year progression-free survival (PFS) was 12%. On univariate analysis, Eastern Cooperative Oncology Group performance status > 0 was predictive of decreased OS (p = 0.0024) and PFS (p = 0.044). Factors predictive of local failure included lower BED (p = 0.016), treatment for recurrence (p = 0.029), and higher pre-treatment SUV (p = 0.026). Kaplan-Meier analysis showed BED ≤35 Gy (p < 0.005) and treatment for recurrence (p = 0.01) to be predictive of local failure. On Cox proportional hazards analysis, treatment of lymph nodes was predictive of complete radiographic response (hazard ratio (HR) = 4.95), as was higher BED (HR = 1.03). Toxicity included 27 cases of grade < 3 toxicity, and one grade 5 late toxicity of GI bleed from a radiation therapy-induced duodenal ulcer.ConclusionsSBRT provides durable local control with minimal toxicity in ovarian cancer, especially with BED > 35 Gy and treatment for lymph nodes.

Hypofractionated vs. conventional radiation therapy for stage III non-small cell lung cancer treated without chemotherapy

Background: Patients with unresectable locally advanced NSCLC who refuse or are not candidates for chemotherapy often receive radiation therapy (RT) alone. Hypofractionated RT (HFRT) regimens are becoming increasingly common. An analysis of the National Cancer Database (NCDB) was performed to evaluate the practice patterns and outcomes of HFRT vs. conventionally fractionated RT (CFRT) in patients with stage III NSCLC undergoing definitive RT alone.Material and methods: The NCDB was queried for all patients with stage III NSCLC diagnosed between 2004 and 2014 who received RT alone. CFRT was defined as patients treated to a total dose of 60–80 Gy in 1.8–2 Gy daily fractions. HFRT was defined as patients treated to a total dose of 50–80 Gy in 2.25–4 Gy fractions. Logistic regression, univariable and multivariable analyses (MVAs) for overall survival (OS) and propensity score matched analyses (PSMAs) were performed.Results: A total of 6490 patients were evaluated: 5378 received CFRT and 1112 received HFRT. Median CFRT dose was 66 Gy in 2 Gy fractions vs. 58.5 Gy in 2.5 Gy fractions for HFRT. HFRT was associated with older age, lower biological effective dose (BED10), academic facility type, higher T-stage and lower N-stage. On initial analysis, HFRT was associated with inferior OS (median 9.9 vs. 11.1 months, p<.001), but after adjusting for the imbalance in covariates such as age, BED10, T-stage and N-stage using PSMA, the difference in survival was no longer significant (p=.1).Conclusions: In the appropriate clinical context, HFRT can be an option for patients with locally advanced NSCLC who are not candidates for chemotherapy or surgical resection. HFRT needs to be further studied in prospective trials to evaluate toxicity and tumor control.

Impact of adjuvant fractionated stereotactic radiotherapy dose on local control of brain metastases.

The aim of this study was to determine whether a higher biological effective dose (BED) would result in improved local control in patients treated with fractionated stereotactic radiotherapy (FSRT) for their resected brain metastases. Patients with newly diagnosed brain metastases without previous brain radiotherapy were retrospectively reviewed. Patients underwent surgical resection of at least one brain metastasis and were treated with adjuvant FSRT, delivering 25-36Gy in 5-6 fractions. Outcomes were computed using Kaplan-Meier survival analysis and univariate analysis. Fifty-four patients with 63 post-operative cavities were included. Median follow-up was 16months (3-60). Median metastasis size at diagnosis was 2.9cm (0.6-8.1) and median planning target volume was 19.7 cm3 (6.3-68.1). Two-year local control (LC) was 83%. When stratified by dose, 2years LC rate was 95.1% in those treated with 30-36Gy in 5-6 fractions (BED10 of 48-57.6 Gy10) versus 59.1% lesions treated with 25Gy in 5 fractions (BED10 of 37.5 Gy10) (p < 0.001). LC was not associated with resection cavity size. One year overall survival was 68.7%, and was independent of BED10. Symptomatic radiation necrosis occurred in 7.9% of patients and was not associated with dose. In the post-operative setting, high-dose FSRT (BED10 > 37.5 Gy10) were associated with a significantly higher rate of LC compared to lower BED regimens. Overall, 25Gy in 5 fractions is not an adequate dose to control microscopic disease. If selecting a 5-fraction regimen, 30Gy in five fractions appears to provide excellent tumor bed control.

Establishment of a Therapeutic Ratio for Gamma Knife Radiosurgery of Trigeminal Neuralgia: The Critical Importance of Biologically Effective Dose Versus Physical Dose

How variations of treatment time affect the safety and efficacy of Gamma Knife (GK) radiosurgery is a matter of considerable debate. With the relative simplicity of treatment planning for trigeminal neuralgia (TN), this question has been addressed in a group of these patients. Using the concept of the biologically effective dose (BED), the effect of the two key variables, dose and treatment time, were considered. A retrospective analysis was performed of 408 TN cases treated from 1997 to 2010. Treatment involved the use of a single 4 mm isocenter. If conditions allowed, the isocenter was placed at a median distance of 7.5 mm from the emergence of the trigeminal nerve from the brain stem. The effects were assessed in terms of the incidence of the complication, hypoesthesia, and in terms of efficacy using the incidence of pain free after 30 days and 1 and 2 years. These responses were evaluated with respect to both the physical dose and the BED, the latter using a bi-exponential repair model. RE-evaluation showed that the prescription doses, at the 100% isodose, varied from 75 to 97.9 Gy, delivered in 25-135 minutes. The relationship between the physical dose and the incidence of hypoesthesia was not significant; the overall incidence was ∼20%. However, a clear relationship was found between the BED and the incidence of hypoesthesia, with the incidence increasing from <5% after a BED of ∼1800 Gy2.47 to 42% after ∼2600 Gy2.47. Efficacy, in terms of freedom from pain, was ∼90%, irrespective of the BED (1550-2600 Gy2.47) at 1 and 2 years. The data suggested that "pain free" status developed more slowly at lower BED values. These results strongly suggest that safety and efficacy might be better achieved by prescribing a specific BED instead of a physical dose. A dose and time to BED conversion table has been prepared to enable iso-BED prescriptions. This finding could dramatically change dose-planning strategies in the future. However, this concept requires validation for other indications for which more complex dose planning is required.

Outcomes Following Radiation for Cutaneous Squamous Cell Carcinoma (cSCC)

Most cases of cutaneous squamous cell carcinoma (cSCC) are cured with surgical excision; however, patients with high-risk features or unresectable tumors are often treated with radiation therapy (RT). Limited data are available to guide adjuvant treatment and estimate risk and patterns of recurrence following RT. We performed a retrospective analysis of cSCC patients treated with RT at 4 affiliated institutions between 1/2007 and 6/2017. Immunosuppression (IS) was defined as patients with organ transplant, heme malignancy/lymphoma, HIV, daily use of >20 mg prednisone (or equivalent) or immunomodulators. Biological Effective Dose (BED) was calculated using alpha/beta = 10. Predictors of recurrence were determined using Chi-squared testing and logistic regression. We identified 105 patients. Median age was 75 years (range 43-102 years); 82% were male and 13% were IS. The most common primary site was scalp (46%) followed by ear (20%), lip (12%) and cheek (12%). Seven (6%) had regional node metastasis. Initial treatment included surgery in 91 (87%) of patients, of which 47 underwent Mohs. Among these 91 patients, 51 (56%) had positive margins, and 47 (45%) had perineural invasion (PNI). Median prescribed RT dose was 60 Gy among 51 patients treated with photons and 58 Gy in 54 patients treated with electrons. Concurrent chemotherapy was administered in 5 (5%) patients, 4 (80%) of whom were treated in the adjuvant setting. With median follow-up of 7 months (range 1-43 months), there were 28 (27%) recurrences. Most of the recurrences were regional (n=17, 16%). There were 9 (9%) in-field, 4 (4%) marginal, and no distant recurrences. On univariate analyses, factors associated with any recurrence were IS (p=0.03) and RT parameters: photon RT (p=0.02), lower dose (p=0.046), decreased number of fractions (p=0.049), and lower BED (p=0.041). Depth of invasion was also marginally inversely associated with risk of recurrence (p=0.045), possibly because patients with increased depth received higher BED treatment (p=0.01). The association between recurrence and IS was driven by in-field failures (7% in non-IS versus 16% in IS) and regional recurrences (13% in non-IS versus 32% in IS). Among the 14 patients who did not receive surgery and were treated with definitive RT, there was 1 in-field failure (7%) in a patient that received hypofractionated RT to 36 Gy in 6 fractions. There were also 1-marginal (7%) and 2 regional (14%) recurrences among the definitive RT patients. We report among the largest experience of outcomes following radiation for cSCC. We find favorable rates of in-field control, even among patients treated with definitive radiation. IS was associated with higher rates of regional and in-field recurrence, suggesting a need for further evaluation of elective nodal treatment and intensification strategies in this high-risk patient population.

Radiotherapy for locally recurrent rectal cancer treated with surgery alone as the initial treatment.

PurposeAlthough the technical developments of radiotherapy have been remarkable, there are currently few reports on the treatment results of radiotherapy for local recurrence of rectal cancer treated with surgery alone as initial treatment in this three-dimensional conformal radiotherapy era. Thus, we retrospectively evaluated the treatment results of radiotherapy for local recurrence of rectal cancer treated with surgery alone as the initial treatment.Materials and MethodsThirty-two patients who underwent radiotherapy were enrolled in this study. The dose per fraction was 2.0–3.5 Gy. Because the treatment schedule was variable, the biological effective dose (BED) was calculated.ResultsLocal control (LC) and overall survival (OS) rates from the completion of radiotherapy were calculated. The 1-, 2-, 3-, 4-, and 5-year LC rates were 51.5%, 24.5%, 19.6%, 19.6%, and 13.1%, respectively. LC rates were significantly higher for the high BED group (≥75 Gy10) than for the lower BED group (<75 Gy10). All patients who reported pain achieved pain relief. The duration of pain relief was significantly higher for the high BED group than for the lower BED group. The 1-, 2-, 3-, 4-, and 5-year OS rates were 82.6%, 56.5%, 45.2%, 38.7%, and 23.2%, respectively. There was a trend toward higher OS rates in with higher BED group compared to lower BED group.ConclusionFor patients with unresectable locally recurrent rectal cancer treated with surgery alone, radiotherapy is effective treatment. The prescribed BED should be more than 75 Gy10, if the dose to the organ at risk is within acceptable levels.

VMAT plus a few computer-optimized non-coplanar IMRT beams (VMAT+) tested for liver SBRT

PurposeTo propose a novel treatment approach, designated VMAT+, involving addition of <5 IMRT beams with computer-optimized non-coplanar orientations to VMAT, and evaluate it for liver Stereotactic Body Radiation Therapy (SBRT). VMAT+ is investigated as an alternative for (1) coplanar VMAT and (2) multi-beam non-coplanar treatment. Methods/materialsFor fifteen patients with liver metastases, VMAT+ plans were compared with (1) dual-arc VMAT and (2) 25-beam, non-coplanar treatment with computer-optimized beam orientations (25-NCP). All plans were generated fully automatically for delivery of the highest feasible tumor Biologically Effective Dose (BED). OAR doses, intermediate-dose-spillage, dose-compactness, and measured delivery times were evaluated. ResultsWith VMAT+ the maximum achievable tumor BED was equal to that of 25-NCP. Conversely, VMAT resulted in a lower tumor BED in 5 patients. Compared to VMAT, VMAT+ yielded significant dose reductions in OARs. Intermediate-dose-spillage and dose-compactness were significantly improved by 9.8% and 17.3% (p≤0.002), respectively. Treatment times with VMAT+ were only enhanced by 4.1min on average, compared to VMAT (8.4min). Improvements in OAR sparing with 25-NCP, compared to VMAT+, were generally modest and/or statistically insignificant, while delivery times were on average 20.5min longer. ConclusionsFor liver SBRT, VMAT+ is equivalent to time-consuming treatment with 25 non-coplanar beams in terms of achievable tumor BED. Compared to VMAT, OAR sparing and intermediate-dose-spillage are significantly improved, with minor increase in delivery time.

Lower mean heart dose with deep inspiration breath hold-whole breast irradiation compared with brachytherapy-based accelerated partial breast irradiation for women with left-sided tumors

PurposeFor left-sided breast cancer, radiation to the heart is a concern. We present a comparison of mean heart and coronary artery biologically effective dose (BED) between accelerated partial breast irradiation (APBI) and whole breast irradiation with deep inspiration breath-hold technique (DIBH-WBI). Methods and materialsA total of 100 patients with left-sided, early-stage breast cancer were identified. Fifty underwent single-entry catheter-based APBI and 50 underwent DIBH-WBI. The heart, left anterior descending/interventricular branch, left main, and right coronary artery were delineated. BEDs were calculated from APBI treatment plans (34 Gy in 3.4 Gy twice daily fractions) and for 4 separate plans generated for each DIBH-WBI patient: 50 Gy in 25 fractions (50/25), 50/25 + 10/5 boost, 40/15, and 40/15 + 10/5 boost. ResultsBED to the heart and coronary vessels were statistically significantly higher with APBI than with any of the DIBH-WBI dose/fractionation schedules. ConclusionsFor women with left-sided early-stage breast cancer, DIBH-WBI resulted in statistically significantly lower mean BED to the heart and coronary vessels compared with APBI. This is likely due to increased physical separation between the heart and tumor bed afforded by the DIBH-WBI technique. Long-term assessment of late effects in these tissues will be required to determine whether these differences are clinically significant.

Stereotactic body radiotherapy for metastatic spinal sarcoma: a detailed patterns-of-failure study.

OBJECTIVE The aim of this study was to report the first detailed analysis of patterns of failure within the spinal axis of patients treated with stereotactic body radiotherapy (SBRT) for sarcoma spine metastases. METHODS Between 2005 and 2012, 88 consecutive patients with metastatic sarcoma were treated with SBRT for 120 spinal lesions. Seventy-one percent of patients were enrolled on prospective institutional protocols. For patients who underwent routine posttreatment total-spine MRI (64 patients, 88 lesions), each site of progression within the entire spinal axis was mapped in relation to the treated lesion. Actuarial rates of local-, adjacent-, and distant-segment failure-free survival (FFS) were calculated using the Kaplan-Meier method. RESULTS The median follow-up for the cohort was 14.4 months, with 81.7% of patients followed up until death. The 12-month actuarial rate of local FFS was 85.9%; however, 83.3% of local failures occurred in conjunction with distant-segment failures. The 12-month actuarial rates of isolated local-, adjacent-, and distant-segment FFS were 98.0%, 97.8%, and 74.7%, respectively. Of patients with any spinal progression (n = 55), only 25.5% (n = 14) had progression at a single vertebral level, with 60.0% (n = 33) having progression at ≥ 3 sites within the spine simultaneously. Linear regression analysis revealed a relationship of decreasing risk of failure with increasing distance from the treated index lesion (R(2) = 0.87), and 54.1% of failures occurred ≥ 5 vertebral levels away. Treatment of the index lesion with a lower biological effective dose (OR 3.2, 95% CI 1.1-9.2) and presence of local failure (OR 18.0, 95% CI 2.1-152.9) independently predicted for distant spine failure. CONCLUSIONS Isolated local- and adjacent-segment failures are exceptionally rare for patients with metastatic sarcoma to the spine treated with SBRT, thereby affirming the treatment of the involved level only. The majority of progression within the spinal axis occurs ≥ 5 vertebral levels away. Thus, total-spine imaging is necessary for surveillance posttreatment.

Is There a Dose Response Relationship With Stereotactic Body Radiation Therapy for Pulmonary Oligometastases?

To determine whether there exists a dose-response relationship for pulmonary oligometastases treated with stereotactic body radiation therapy (SBRT). An Institutional Review Board (IRB)-approved registry of patients treated with stereotactic body radiation therapy (SBRT) was queried for patients with oligometastatic disease who were treated with SBRT to the lung between 2004 and 2014. Demographic information, comorbidities, size of lesion, number of pulmonary metastases, histology of primary cancer, PET SUV of lesion, use and timing of chemotherapy, and dosimetric parameters were recorded. Local failure was defined as persistent growth of the treated lesion on subsequent imaging, increasing SUV after treatment, or biopsy-proven recurrence. Local control (LC) and overall survival (OS) were calculated using actuarial analysis. LC was stratified by fractionation based on biological effective dose (BED) grouping (100-105 Gy vs 120-132 Gy vs 180 Gy). Cox proportional hazards regression was used to identify factors associated with LC and OS. Eighty-nine patients (pts) with 140 lesions were treated during this time period. The median age was 65.9 years (yr). Median follow-up was 24.6 months. 24 pts (28.1%) had colorectal primaries. Other common histologies were sarcoma (18 pts, 20.2%) head and neck (10 pts, 11.2%), and non-small cell lung cancer (8 pts, 9.0%). Breast, esophageal, GYN, melanoma, pancreaticobiliary, renal cell, thyroid, and other histologies comprised the remainder. Chemotherapy was not given in 21 pts (23.6%), pre- and post-SBRT in 31 pts (34.8%), pre-SBRT in 32 pts (36.0%), and post-SBRT in 4 pts (4.5%). 105 lesions (75.0%) were treated with BED 100-105.6 Gy, 13 lesions (7.8%) were treated with BED 120-132 Gy, 17 lesions (12.1%) were treated with BED 180 Gy. The overall 2 yr rate of LC was 79.5% (81.0% for BED 100-105, 50% for BED 120-132, and 91.3% for BED 180). Differences were not statistically significant. On multivariate analysis, colorectal primary was associated with worse LC (HR 2.92, 95%CI 1.200-7.092). Overall 2 yr OS was 68.7% (66.9% for BED 100-105, 81.8% for BED 120-132, and 75.7% for BED 180). Lower BED (100-105 Gy vs 180 Gy) was the only factor associated with worse OS on univariate analysis (HR 2.82, 95% CI 1.080-7.351). SBRT with higher BED trended towards improved LC and was associated with improved survival compared to lower BED. Colorectal oligometastases are associated with worse LC than other histologies. Further multi-institutional collaboration is needed to validate these findings and to determine optimal SBRT doses for oligometastases by histology.

The role of the concept of biologically effective dose (BED) in treatment planning in radiosurgery

Radiosurgery (RS) treatment times vary, even for the same prescription dose, due to variations in the collimator size, the number of iso-centres/beams/arcs used and the time gap between each of these exposures. The biologically effective dose (BED) concept, incorporating fast and slow components of repair, was used to show the likely influence of these variables for Gamma Knife patients with Vestibular Schwannomas. Two patients plans were selected, treated with the Model B Gamma Knife, these representing the widest range of treatment variables; iso-centre numbers 3 and 13, overall treatment times 25.4 and 129.6 min, prescription dose 14 Gy. These were compared with 3 cases treated with the Perfexion® Gamma Knife. The iso-centre number varied between 11 and 18, treatment time 35.7 – 74.4 min, prescription dose 13 Gy. In the longer Model B Gamma Knife treatment plan the 14 Gy iso-dose was best matched by the 58 Gy2.47 iso-BED line, although higher and lower BED values were associated with regions on the prescription iso-dose. The equivalent value for the shorter treatment was 85 Gy2.47. BED volume histograms showed that a BED of 85 Gy2.47 only covered ∼65% of the target in the plan with the longer overall treatment time. The corresponding BED values for the 3 cases, treated with the Perfexion® Gamma Knife, were 59.5, 68.5 and 71.5 Gy2.47.In conclusion BED calculations, taking account of the repair of sublethal damage, may indicate the importance of reporting overall time to reflect the biological effectiveness of the total physical dose applied.

Stereotactic body radiotherapy for re-irradiation of lung cancer recurrence with lower biological effective doses.

ObjectiveFew studies have evaluated re-irradiation of lung cancer recurrences with stereotactic body radiotherapy (SBRT). This study evaluates outcomes with SBRT re-irradiation for recurrent lung cancer.MethodsTwo hundred and seventy-eight patients treated with SBRT for lung cancer were retrospectively reviewed. Of those, 26 patients with 29 tumors were re-irradiated with SBRT. Ninety percent of tumors received prior external beam irradiation and 10 % received prior SBRT. Previous median radiation dose was 61.2 Gy with a median 8-month interval from previous radiation. The median re-irradiation SBRT dose was 30 Gy (48 Gy10 biological effective dose (BED)). Endpoints evaluated included local control, overall survival, and progression-free survival.ResultsTwenty-five of 29 tumors were evaluable for local control, with 27 tumors (93 %) considered in-field recurrences. In-field crude local control rate was 80 % (20/25) with 1 and 2-year actuarial rates of 78.6 and 65.5 %, respectively. One and 2-year actuarial survival rates were 52.3 and 37.0 %, respectively. One and 2-year actuarial progression-free survival rates were 56.7 and 37.0 %, respectively. Fifty-five percent of patients reported acute/chronic grades 1 and 2 toxicities. No grade 3 or higher toxicities were reported.ConclusionPatients with recurrent lung cancer have limited options. SBRT re-irradiation is tolerable even after a median 61.2 Gy to the re-irradiation site. The lower BED used provided acceptable progression-free survival with low toxicity. Given the poor prognosis with current treatment options, new paradigms for re-treatment should include SBRT-re-irradiation as an adjunct to systemic therapy for in-field lung cancer recurrence.

SU-E-T-147: Efficacy of Prostate SBRT When the Daily Anatomy Differs Significantly From the Baseline Anatomy

Purpose: To determine the effects of interfraction motion on the efficacy of prostate SBRT when the daily anatomy differs significantly from the baseline anatomy. Methods: A daily CBCT was acquired for a patient who was treated with 44–1.8 Gy fractions of a VMAT plan from Varian's Eclipse treatment planning system. This plan was then escalated into 2 hypofractionated regimes (4.3 Gy for 12 fractions and 7.25 Gy for 5 fractions) and applied to all datasets collected. For one particular fraction, the prostate anatomy was found to be significantly different from the simulated anatomy. A VMAT plan was created for this outlier dataset that had identical dosimetric goals as the original 44-fraction plan. This plan was also escalated into 2 hypofractionated regimes and applied to all datasets. To make comparisons between all plans, the biologically effective dose (BED) was calculated for each fraction for the bladder, rectum, and prostate. To increase the statistical significance of the average BED for each structure, the 44 individual fractions were uniquely combined for the hypofractionated regimes resulting in 21,090,682,613 instances of 4.3 Gy/fraction regiments and 1,086,008 instances of 7.25 Gy/fraction regiments. Results: Despite the large difference between the simulated and daily anatomy, the plan created from the outlier dataset resulted in a higher average BED for the prostate and a lower average BED for the rectum when compared to the original plan. The average BED for the bladder increased for the plan created from the outlier dataset. The BEDs varied more for the normal tissues than for the target when the daily anatomy was significantly different from the baseline. Conclusion: SBRT is still a viable option even when the daily anatomy differs significantly from the baseline anatomy. The dose to the prostate was not negatively affected, while the dose to the rectum improved.

Biologically effective dose and definitive radiation treatment for localized prostate cancer

It is not clear if prolongation of definitive external radiation therapy for prostate cancer has an effect on biochemical failure. The aim of this work was to evaluate whether the biologically effective dose (BED), and in particular the duration of radiotherapy, intended as overall treatment time, has an effect on biochemical failure rates and to develop a nomogram useful to predict the 6-year probability of biochemical failure. A total of 670 patients with T1-3 N0 prostate cancer were treated with external beam definitive radiotherapy, to a total dose of 72-79.2 Gy in 40-44 fractions. The computed BED values were treated with restricted cubic splines. Variables were checked for colinearity using Spearman's test. The Kaplan-Meier method was used to calculate freedom from biochemical relapse (FFBR) rates. The Cox regression analysis was used to identify prognostic factors of biochemical relapse in the final most performing model and to create a nomogram. Concordance probability estimate and calibration methods were used to validate the nomogram. Neoadjuvant and concomitant androgen deprivation was administered to 475 patients (70%). The median follow-up was 80 months (range 20-129 months). Overall, the 6-year FFBR rate was 88.3%. BED values were associated with higher biochemical failure risk. Age, iPSA, risk category, and days of radiotherapy treatment were independent variables of biochemical failure. A prolongation of RT (lower BED values) is associated with an increased risk of biochemical failure. The nomogram may be helpful in decision making for the individual patient.